Modern resuscitation has many components – emphasis on pre-hospital CPR, distribution of defibrillators, cardiac catheterization ... and hypothermia. And, now we're not so sure about that last one.
Therapeutic hypothermia is based on two randomized trials, published in 2002, enrolling a grand total of 352 patients. Recommendations include rapid cooling after emergency stabilization to a target temperature between 32° and 34°C, and subsequent adoption of this practice spawned a cottage industry of expensive, specialized cooling devices. But, these temperature targets were always somewhat arbitrary, and the question persisted as to whether lower temperatures in fact conferred a neurologic survival advantage.
Enrolling nearly a thousand patients, this randomized trial of out-of-hospital cardiac arrest randomized half to 33°C and half to 36°C. Groups were well-balanced on typically expected features favoring survival – comorbidities, bystander CPR, arrest rhythm, and follow-up treatment. And, after cooling for 24 hours, no difference was detected in early deaths, late deaths, or in any measure of cerebral or functional performance. One impressive feature of this trial is the standardized withdrawal of care criteria, reducing patient heterogeneity through that mechanism.
None of this says "hypothermia doesn't work". But, a sense of lacking in terms of a dose-response relationship between hypothermia and neurologic survival causes some concern. Why did we observe such profound benefit in the early trials? Erroneous rejection of the null hypothesis due to poor statistical power, unmeasured confounders, or something more sinister? Adding in the pre-hospital hypothermia study from JAMA, both dose-dependent and time-dependent effects are now less certain.
The utility of hypothermia following ischemic insult seems biologically plausible, but, as the editorial comments, perhaps it's not so much hypothermia as the maintenance of normothermia. Already part of modern post-stroke care, treating and preventing fever improves outcomes – it may simply be the observed benefits are due to intensive antipyresis, rather than hypothermia.
It seems still reasonable to use gentle cooling as a prophylaxis against hyperthermia, but more importantly, it is time, yet again, to reflect on how better evidence refines established practice. Without continuing to recognize the limitations of our knowledge, we must caution ourselves against rushing to generalize implementation from small sample sizes (see: tPA in acute ischemic stroke).
"Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest"
"Temperature Management and Modern Post–Cardiac Arrest Care"